Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUSATXO)

• DOT Name: G-protein coupled receptor 55 (GPR55)
• Gene Name: GPR55
• UniProt ID: GPR55_HUMAN
• Pfam ID: PF00001
• Sequence:
  MSQQNTSGDCLFDGVNELMKTLQFAVHIPTFVLGLLLNLLAIHGFSTFLKNRWPDYAATS
  IYMINLAVFDLLLVLSLPFKMVLSQVQSPFPSLCTLVECLYFVSMYGSVFTICFISMDRF
  LAIRYPLLVSHLRSPRKIFGICCTIWVLVWTGSIPIYSFHGKVEKYMCFHNMSDDTWSAK
  VFFPLEVFGFLLPMGIMGFCCSRSIHILLGRRDHTQDWVQQKACIYSIAASLAVFVVSFL
  PVHLGFFLQFLVRNSFIVECRAKQSISFFLQLSMCFSNVNCCLDVFCYYFVIKEFRMNIR
  AHRPSRVQLVLQDTTISRG
• Function: G-protein coupled receptor that binds to several ligands including 2-arachidonoyl lysophosphatidylinositol or lysophosphatidylglucoside with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Induces the Ca(2+) release from intracellular stores via ERK, the heterotrimeric G protein GNA13 and RHOA leading to morphological changes including cell rounding and stress fiber formation. In macrophages, acts downstream of lysophosphatidylglucoside to inhibit the translocation of the phospholipid-transporting ABCA1 to plasma membrane and subsequent cholesterol efflux leading to lipid accumulation and foam cell formation.
• Tissue Specificity: Expressed in the caudate nucleus and putamen, but not detected in the hippocampus, thalamus, pons cerebellum, frontal cortex of the brain or in the liver. Expressed in osteoclasts and osteoblasts. Higly expressed in macrophages and B-cells .
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

Molecular Interaction Atlas (MIA) of This DOT

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of G-protein coupled receptor 55 (GPR55).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of G-protein coupled receptor 55 (GPR55).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of G-protein coupled receptor 55 (GPR55).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of G-protein coupled receptor 55 (GPR55).	[5]
AM251	DMTAWHL	Investigative	AM251 increases the activity of G-protein coupled receptor 55 (GPR55).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of G-protein coupled receptor 55 (GPR55).	[4]

References

• [1] Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide. Arch Dermatol Res. 2017 May;309(4):285-303. doi: 10.1007/s00403-017-1729-0. Epub 2017 Mar 11.
• [2] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [3] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Selective GPR55 antagonism reduces chemoresistance in cancer cells. Pharmacol Res. 2016 Sep;111:757-766. doi: 10.1016/j.phrs.2016.07.013. Epub 2016 Jul 14.